The central theme of CDART is that multiple facets of impulsivity defined by the UPPS scale of Whiteside and Lynam (2001) are related to different paths to drug use and that these paths are associated with different neurobiological mechanisms. To the extent that we can link specific behavioral tasks to these different self-report facets, animal models can be used to identify critical neural mechanisms that undedie the association between risk-related facets and drug use. A detailed understanding of the mechanisms that mediate the link between different facets of impulsivity and drug use will provide information about designing preventive interventions that target these risk-related facets. The overall goal of this preclinical project is to test two overarching hypotheses: (1) individual differences in the facets termed urgency, disinhibition and sensation seeking are related most strongly to problem use, escalation and initiation respectively, as operationally defined within an animal model of drug self- administration; and (2) individual differences in urgency, disinhibition and sensation seeking are related most strongly to differences in amygdala, prefrontal cortex and nucleus accumbens respectively, as measured by in vitro neurochemistry and in vivo electrophysiology. The specific aims are to: Aim 1: Develop an animal model of urgency using a task similar to that developed in humans. Aim 2: Determine if individual differences in urgency, disinhibition and sensation seeking predict problem use, escalation and/or initiation of amphetamine self-administration, respectively. Aim 3: Determine if individual differences in facets of impulsivity differentially predict the ability of nondrug interventions to reduce use, escalation and/or initiation of amphetamine self-administration. Aim 4: Determine if individual differences in these risk-related facets of impulsivity are related to alterations in monoamine transporter function in amygdala, prefrontal cortex and/or nucleus accumbens. Aim 5: Determine if individual differences in these risk-related facets of impulsivity are related to altered patterns of neuronal activity in amygdala, prefrontal cortex and/or nucleus accumbens. RELEVANCE (See instructions): Anti-drug preventive interventions may be most effective if they are designed to target those at highest nsk. The current project will explore the basic neurobehavioral mechanisms that mediate risk. The long- term goal is to translate these basic research findings into the design of targeted biologically-relevant preventive interventions that can be evaluated in field studies.